Rotaviruses are the major cause of severe diarrhea in infants and young children in both developed and developing countries. Therefore, intensive efforts are being made to develop an effective vaccine. Two outer capsid rotavirus proteins, VP7 or VP4, are each associated with the induction of neutralizing antibodies that have been shown in experimental animals to be associated with resistance to illness. Serotype specificity has been associated with VP7. However, recent studies have begun to elucidate the antigenic relationships among human rotaviruses based on the antigenic specificity of the VP4 protein as well. Human rotavirus strains that were associated with symptomatic infection and that exhibited VP7 specificity of serotype 1, 2, 3, 4, or 9 each possessed a similar VP4 as determined by neutralization assay. We have chosen the outer capsid protein VP4 of porcine rotavirus OSU as a model to study the immunogenicity of this protein in an adenovirus vector. The ability of adenovirus to be administered orally makes the potential use of adenovirus vectors for vaccine production particularly attractive. In addition, adenovirus vaccines have already been shown to be safe in humans when administered orally as enteric coated capsules or tablets.